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Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease

Cunningham, C., Deacon, R., Wells, H., Boche, D., Waters, E., Picanco Diniz, C., Scott, H., Rawlins, JNP. and Perry, VH. (2003) Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease European Journal of Neuroscience, 17, (10), pp. 2147-2155. (doi:10.1046/j.1460-9568.2003.02662.x).

Record type: Article

Abstract

Prion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized byamyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J mouse, we have shown previously that these animals display behavioural changes that indicate the onset of neuronal dysfunction. The current study examines the neuropathological correlates of these early behavioural changes. After injection of ME7-infected homogenate into the dorsal hippocampus, we found statistically significant impairment of burrowing, nesting and glucose consumption, and increased open field activity at 13 weeks. At this time, microglia activation and PrPSc deposition was visible selectively throughout the limbic system, including the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies, dorsal thalamus and, to a lesser degree, in regions of the brainstem. No increase in apoptosis or neuronal cell loss was detectable at this time, while in animals at 19 weeks postinjection there was 40% neuronal loss from CA1. There was a statistically significant reduction in synaptophysin staining in the stratum radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage to the dorsal hippocampus is known to disrupt burrowing and nesting behaviour. We have demonstrated a neuropathological correlate of an early behavioural deficit in prion disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases.

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Published date: May 2003
Keywords: hippocampus, neurodegeneration, neuronal dysfunction, scrapie, synapse

Identifiers

Local EPrints ID: 23975
URI: http://eprints.soton.ac.uk/id/eprint/23975
ISSN: 0953-816X
PURE UUID: b79d81e8-17a8-4ad0-b990-799552d8c0b3
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 17 Mar 2006
Last modified: 17 Jul 2017 16:15

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Contributors

Author: C. Cunningham
Author: R. Deacon
Author: H. Wells
Author: D. Boche ORCID iD
Author: E. Waters
Author: C. Picanco Diniz
Author: H. Scott
Author: JNP. Rawlins
Author: VH. Perry

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